Version July 2025
Myocardial damage, including acute left ventricular failure, can occur with epirubicin. The risk of cardiomyopathy is proportional to the cumulative exposure, with incidence rates from 0.9% at a cumulative dose of 550 mg/m2, 1.6% at 700 mg/m2, and 3.3% at 900 mg/m2. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction before and regularly during and after treatment with epirubicin.
Secondary acute myeloid leukemia and myelodysplastic syndrome occur at a higher incidence in patients treated with anthracyclines, including epirubicin.
Extravasation of epirubicin may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area.
Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur.
Dosage guidance:
Safety: If clinically reasonable, delay epirubicin therapy until other cardiotoxic agents with long half-lives (eg, trastuzumab) have been cleared. A lifetime maximum cumulative epirubicin dose ≥900 mg/m2 should be avoided. Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (Ref).
Clinical considerations : Patients receiving 120 mg/m2/cycle IV as part of combination therapy (CEF-120 regimen) should receive prophylactic antibiotic therapy. Epirubicin IV is associated with a moderate or high emetic potential (depending on regimen); antiemetics are recommended to prevent nausea and vomiting (Ref). Hydration and antihyperuricemic prophylaxis may minimize potential tumor lysis syndrome. Please refer to the protocol or institutional guidance for additional details of off-label dosing.
Bladder cancer, non–muscle invasive (off-label use): Intravesical instillation: 50 or 80 mg as a single instillation (retained for 1 hour) within 6 hours postoperatively after transurethral resection (Ref).
Breast cancer, adjuvant treatment: Note: Consider lower starting doses (75 to 90 mg/m2) in heavily treated patients and in patients with preexisting bone marrow depression or with neoplastic bone marrow infiltration.
Usual dose: IV: 100 to 120 mg/m2 per 3- or 4-week treatment cycle as follows:
CEF-120 regimen: IV: 60 mg/m2 on days 1 and 8 every 28 days for 6 cycles in combination with cyclophosphamide and fluorouracil (Ref).
FEC-100 regimen: IV: 100 mg/m2 on day 1 every 21 days for 6 cycles in combination with cyclophosphamide and fluorouracil (Ref).
Breast cancer (off-label regimens):
EC regimen (adjuvant therapy): IV: 100 mg/m2 on day 1 every 21 days for 8 cycles in combination with cyclophosphamide (Ref).
FEC regimen ± paclitaxel (adjuvant therapy): IV: 90 mg/m2 on day 1 every 21 days for 6 cycles in combination with fluorouracil and cyclophosphamide or for 4 cycles in combination with fluorouracil and cyclophosphamide followed by paclitaxel (Ref).
FEC regimen followed by pertuzumab + trastuzumab + docetaxel (neoadjuvant therapy): IV: 100 mg/m2 on day 1 every 21 days for 3 cycles in combination with fluorouracil and cyclophosphamide, followed by 3 cycles of pertuzumab, trastuzumab, and docetaxel (Ref).
Keynote-522 regimen (early triple-negative breast cancer; neoadjuvant therapy): IV: 90 mg/m2 once every 3 weeks (in combination with cyclophosphamide [EC] and pembrolizumab) for 4 cycles (second neoadjuvant treatment); first neoadjuvant treatment was 4 cycles of pembrolizumab/paclitaxel/carboplatin, followed by second neoadjuvant treatment of 4 cycles of EC plus pembrolizumab. After definitive surgery, patients received adjuvant therapy with pembrolizumab and radiation for up to 9 cycles (Ref).
EP or EC regimen (first-line therapy for metastatic disease): IV: 75 mg/m2 on day 1 every 21 days for up to 6 cycles in combination with either paclitaxel or cyclophosphamide (Ref).
EC regimen (first-line therapy for metastatic disease): IV: 60 to 90 mg/m2 on day 1 every 21 days (in combination with cyclophosphamide); continue until disease progression, unacceptable toxicity, or until the maximum cumulative anthracycline dose is reached (Ref).
CEF regimen (first-line therapy for metastatic disease): IV: 50 mg/m2 on days 1 and 8 every 21 or 28 days for 6 to 9 cycles in combination with cyclophosphamide and fluorouracil (Ref).
Peripheral T-cell lymphoma, enteropathy associated (off-label use): Note: One course of CHOP chemotherapy is administered beginning on day 1.
IV: 50 mg/m2 on days 21, 49, and 77 (in combination with ifosfamide, mesna, and etoposide [IVE regimen], and alternating with methotrexate and leucovorin) followed by autologous hematopoietic cell transplantation ~4 to 6 weeks following the last course of IVE/methotrexate (Ref).
Soft tissue sarcoma (off-label use):
Adjuvant therapy : IV: 25 mg/m2 on days 1, 2, and 3 every 28 days (in combination with ifosfamide and mesna) for 4 cycles (Ref) or 60 mg/m2 on days 1 and 2 every 21 days (in combination with ifosfamide, mesna, and filgrastim) for 5 cycles (Ref).
Neoadjuvant followed by adjuvant therapy: IV: 30 mg/m2 on days 1 to 4 every 21 days (in combination with ifosfamide and mesna) in neoadjuvant cycles 1 and 3 (epirubicin was omitted in cycle 2 and external beam radiation was administered cycle 2), followed by 30 mg/m2 on days 1 to 4 every 21 days (in combination with ifosfamide and mesna) for 3 adjuvant cycles (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate kidney function impairment (serum creatinine <5 mg/dL): There are no dosage adjustments provided in the manufacturer’s labeling, however, no significant epirubicin pharmacokinetic alterations have been observed in patients with a serum creatinine <5 mg/dL).
Severe kidney function impairment (serum creatinine >5 mg/dL): Consider lower doses (dose not specified) (Ref).
Dialysis: Epirubicin has not been studied in patients on dialysis.
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times ULN: Administer 50% of recommended starting dose (Ref).
Bilirubin >3 mg/dL or AST >4 times ULN: Administer 25% of recommended starting dose (Ref).
Severe hepatic impairment (Child-Turcotte-Pugh class C or serum bilirubin >5 mg/dL): Use is contraindicated (Ref).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Hematologic toxicity (in breast cancer, adjuvant therapy):
Delay day 1 dose of subsequent cycles until platelets are ≥100,000/mm3, ANC ≥1,500/mm3, and nonhematologic toxicities have recovered to ≤ grade 1.
Reduce day 1 dose in subsequent cycles to 75% of previous day 1 dose if patient experiences nadir platelet counts <50,000/mm3, ANC <250/mm3, neutropenic fever, or grade 3/4 nonhematologic toxicity during the previous cycle.
For CEF-120 regimen, reduce day 8 dose to 75% of day 1 dose if platelet counts are 75,000 to 100,000/mm3 and ANC is 1,000 to 1,499/mm3; omit day 8 dose if platelets are <75,000/mm3, ANC <1,000/mm3, or grade 3/4 nonhematologic toxicity.
Nonhematologic toxicity:
Cardiotoxicity: Discontinue epirubicin if signs/symptoms of cardiomyopathy develop. Consider discontinuation if left ventricular ejection fraction decreases or if signs/symptoms of heart failure develop. Consider dexrazoxane (if appropriate) to reduce cardiac toxicity in patients who have received a high cumulative dose of anthracycline therapy (Ref).
Asymptomatic cardiac dysfunction : Consider initiating heart failure medications (eg, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and/or beta blockers) in patients with asymptomatic (stage B) heart disease (Ref).
Mild cardiac dysfunction: Continue treatment with close cardiovascular monitoring (Ref).
Moderate or severe cardiac dysfunction: Interrupt treatment and utilize a multidisciplinary approach when deciding if/when to restart. Initiation of heart failure medications is recommended (Ref).
Symptomatic cardiac dysfunction: Initiate heart failure medications (Ref).
Mild cardiac dysfunction: Consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation (Ref).
Moderate cardiac dysfunction: Interrupt treatment; consider a multidisciplinary approach for decisions regarding treatment reinitiation (Ref).
Severe cardiac dysfunction: Discontinue anthracycline therapy (Ref).
Epirubicin plasma clearance was reduced by 35% in female patients >70 years of age. Although no initial dosage reduction is specifically recommended, particular care should be exercised in monitoring toxicity and adjusting subsequent dosage in females >70 years of age.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not always defined. Percentages reported as part of combination chemotherapy regimens.
Cardiovascular: Decreased left ventricular ejection fraction (asymptomatic; delayed: 1% to 2%), cardiac failure (≤2%), atrioventricular block, bradycardia, bundle branch block, cardiac arrhythmia, cardiomyopathy, ECG abnormality, myocarditis, non-specific T wave on ECG, sinus tachycardia, ST segment changes on ECG, tachyarrhythmia, thromboembolism, ventricular premature contractions, ventricular tachycardia
Central nervous system: Lethargy (1% to 46%)
Dermatologic: Alopecia (70% to 96%), skin rash (1% to 9%), skin changes (1% to 5%)
Endocrine & metabolic: Amenorrhea (69% to 72%), hot flash (5% to 39%)
Gastrointestinal: Nausea and vomiting (83% to 92%; grades 3/4: 22% to 25%), mucositis (9% to 59%; grades 3/4: ≤9%), diarrhea (7% to 25%), anorexia (2% to 3%), abdominal pain, esophagitis, neutropenic enterocolitis, stomatitis, toxic megacolon
Genitourinary: Menopause (premature or early)
Hematologic & oncologic: Neutropenia (54% to 80%; grades 3/4: 11% to 67%; nadir: 10 to 14 days; recovery: by day 21), leukopenia (50% to 80%; grades 3/4: 2% to 59%), anemia (13% to 72%; grades 3/4: ≤6%), thrombocytopenia (5% to 49%; grades 3/4: ≤5%), febrile neutropenia (grades 3/4: ≤6%), acute lymphocytic leukemia, acute myelocytic leukemia, myelodysplastic syndrome
Hepatic: Ascites, hepatomegaly, increased serum transaminases
Hypersensitivity: Hypersensitivity reaction
Infection: Infection (15% to 22%; grades 3/4: ≤2%)
Local: Injection site reaction (3% to 20%; grades 3/4: <1%)
Ophthalmic: Conjunctivitis (1% to 15%)
Respiratory: Dyspnea, pulmonary edema
Miscellaneous: Fever (1% to 5%)
<1%, postmarketing, case reports: Anaphylaxis, arterial embolism, burning sensation of gastrointestinal tract, chills, dehydration, erythema, flushing, gastrointestinal erosion, gastrointestinal hemorrhage, gastrointestinal pain, gastrointestinal ulcer, hyperuricemia, nail hyperpigmentation, oral mucosa hyperpigmentation, phlebitis, pneumonia, pulmonary embolism, radiation recall phenomenon, red urine discoloration, sepsis, shock, skin hyperpigmentation, skin photosensitivity, thrombophlebitis, urticaria
Severe hypersensitivity to epirubicin, other anthracyclines, anthracenediones, or any component of the formulation; severe myocardial insufficiency, recent myocardial infarction, or severe arrhythmias; previous treatment with anthracyclines up to the maximum cumulative dose; severe persistent drug-induced myelosuppression; severe hepatic impairment (Child-Pugh class C or serum bilirubin >5 mg/dL).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in the US labeling): Marked persistent myelosuppression induced by prior treatment with other chemotherapy agents or by radiotherapy.
Concerns related to adverse effects:
• Bone marrow suppression: Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur. Leukopenia, neutropenia, thrombocytopenia, and anemia may occur.
• Cardiac toxicity: Myocardial damage, including acute left ventricular failure, can occur with epirubicin. The risk of cardiomyopathy is proportional to the cumulative exposure, with incidence rates from 0.9% at a cumulative dose of 550 mg/m2, 1.6% at 700 mg/m2, and 3.3% at 900 mg/m2. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Early toxicity may consist of sinus tachycardia and/or ECG changes, such as nonspecific ST-T wave changes. Tachycardia, including premature ventricular contractions and ventricular tachycardia, as well as bradycardia, have occurred. Atrioventricular and bundle-branch block have also been reported. These early cardiotoxicities are not necessarily predictive of subsequent delayed cardiotoxicity and are not necessarily a reason to suspend epirubicin therapy. Delayed cardiotoxicity is typically caused by cardiomyopathy, which presents as decreased left ventricular ejection fraction (LVEF) and/or signs/symptoms of heart failure. Delayed cardiotoxicity typically develops late during epirubicin therapy, or within 2 to 3 months after completion of epirubicin; cardiotoxicity has been reported several months to years after therapy termination. The recommended lifetime epirubicin cumulative dose is 900 mg/m2; avoid cumulative doses above this. Total cumulative dose should take into account prior treatment with other anthracyclines or anthracenediones, previous or concomitant treatment with other cardiotoxic agents, or irradiation of chest. Although the risk increases with cumulative dose, irreversible cardiotoxicity may occur at any dose level. Active or dormant cardiovascular disease, concurrent or recent administration of cardiotoxic drugs, prior therapy with other anthracyclines or anthracenediones, or prior or concurrent chest (mediastinal/pericardial area) irradiation may increase the risk of developing late cardiac toxicity. Children may be at increased risk for developing acute and/or delayed cardiotoxicity. The half-life of other cardiotoxic agents (eg, trastuzumab) must be considered in sequential therapy.
According to ASCO guidelines (ASCO [Armenian 2017]), the risk of cardiac dysfunction is increased with high-dose anthracycline therapy (eg, equivalent to doxorubicin ≥250 mg/m2); high-dose radiotherapy (≥30 Gy) with the heart in the treatment field; lower-dose anthracyclines (eg, equivalent to doxorubicin <250 mg/m2) in combination with lower-dose radiotherapy (<30 Gy) with the heart in the treatment field; lower-dose anthracyclines AND any of the following risk factors: ≥2 cardiovascular risk factors (including smoking, hypertension, diabetes, dyslipidemia, and obesity) during or after completion of therapy or ≥60 years of age at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment; treatment with lower-dose anthracycline followed by trastuzumab (sequential therapy); other risk factors for anthracycline-induced cardiotoxicity include age ≥60 years at time of treatment and 2 or more cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment.
• Extravasation: Extravasation of epirubicin may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. If extravasation occurs, immediately terminate administration and apply ice to the affected area. Local tissue injury may manifest as blistering, ulceration, or necrosis. Consider extravasation if burning/stinging occurs during infusion, or if other signs indicating perivenous infiltration or extravasation are present; extravasation may occur even when blood return is present on aspiration, or in patients without burning/stinging symptoms. Injection into a small vein or repeated administration in the same vein may result in venous sclerosis. Avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If perivenous infiltration occurs, immediately discontinue infusion and restart in another vein. If appropriate, dexrazoxane may be considered (if within 6 hours of extravasation).
• Secondary malignancy: Secondary acute myelogenous leukemia and myelodysplastic syndrome occur at a higher incidence in patients treated with anthracyclines, including epirubicin. The latency period for secondary leukemias may be short (1 to 3 years).
• Thromboembolic events: Thrombophlebitis and thromboembolic phenomena (including pulmonary embolism) have occurred; some cases have been fatal. Local phlebitis or thrombophlebitis may be preceded by facial flushing and erythematous streaking along the vein (may be indicative of excessively rapid administration).
• Tumor lysis syndrome: Epirubicin may cause tumor lysis syndrome (TLS), particularly in patients with rapid tumor proliferation.
Special populations:
• Older age: Females ≥70 years of age should be closely monitored for toxicity due to the possibility of decreased epirubicin clearance.
• Pediatric: Children may be at increased risk for developing acute and delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended.
• Radiation recipients: Epirubicin may increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including cutaneous and pulmonary toxicity, may occur in patients who receive epirubicin after prior radiation therapy.
Other warnings/precautions:
• Immunizations: Patients should not be immunized with live or live-attenuated viral vaccines during or shortly after treatment; serious or fatal infection may result in immunocompromised patients. Inactivated vaccines may be administered; however, response may be diminished.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as hydrochloride [preservative free]:
Ellence: 50 mg/25 mL (25 mL); 200 mg/100 mL (100 mL)
Generic: 50 mg/25 mL (25 mL [DSC]); 200 mg/100 mL (100 mL [DSC])
Yes
Solution (Ellence Intravenous)
50 mg/25 mL (per mL): $2.31
200 mg/100 mL (per mL): $2.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 2 mg/mL (5 mL, 25 mL, 100 mL)
Epirubicin is associated with a moderate or high emetic potential (depending on regimen); antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: Infuse over 15 to 20 minutes or slow IV push; if lower doses due to dose reduction are administered, may reduce infusion time proportionally. Do not infuse over <3 minutes. Infuse into a free-flowing IV solution (NS or D5W). Avoid the use of veins over joints or in extremities with compromised venous or lymphatic drainage.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (Ref); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Dexrazoxane: 1,000 mg/m2 (maximum dose: 2,000 mg) IV (administer in a large vein remote from site of extravasation) over 1 to 2 hours days 1 and 2, then 500 mg/m2 (maximum dose: 1,000 mg) IV over 1 to 2 hours day 3; begin within 6 hours of extravasation. Day 2 and day 3 doses should be administered at approximately the same time (± 3 hours) as the dose on day 1 (Ref). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (Ref).
Intravesicular administration (off-label use): Instill into bladder and retain for 1 hour (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Breast cancer, adjuvant treatment: Adjuvant therapy component for primary breast cancer in patients with evidence of axillary node tumor involvement.
Bladder cancer, non–muscle-invasive; Soft tissue sarcoma; Peripheral T-cell lymphoma, enteropathy associated
EpiRUBicin may be confused with DAUNOrubicin, DOXOrubicin, eriBULin, IDArubicin, valrubicin
Ellence [US] may be confused with Elase brand name for dornase alfa [Chile, France, Malaysia]
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Ado-Trastuzumab Emtansine: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider Therapy Modification
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bevacizumab: May increase cardiotoxic effects of Anthracyclines. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cimetidine: May increase serum concentration of EpiRUBicin. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloPHOSphamide: May increase cardiotoxic effects of Anthracyclines. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fam-Trastuzumab Deruxtecan: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider Therapy Modification
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Margetuximab: Anthracyclines may increase adverse/toxic effects of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Taxane Derivatives: May increase adverse/toxic effects of Anthracyclines. Specifically, the risk of cardiotoxicity may be increased with this combination. Taxane Derivatives may increase serum concentration of Anthracyclines. Management: Administer doxorubicin before paclitaxel, administer idarubicin after paclitaxel has been stopped for 5 half lives, consider use of liposomal doxorubicin, epirubicin, or docetaxel instead of doxorubicin/paclitaxel. Monitor for cardiovascular toxicities. Risk D: Consider Therapy Modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Trastuzumab: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider Therapy Modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during treatment and for 6 months after the last dose of epirubicin. Patients with partners who are pregnant should use condoms during treatment and for at least 7 days after the last epirubicin dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last dose of epirubicin.
Epirubicin may cause amenorrhea and premature menopause; recovery of menses and ovulation is dependent upon age at treatment. Epirubicin may also cause azoospermia, oligospermia, and permanent loss of fertility. Sperm counts may return to normal in some patients and may occur several years after the last dose of epirubicin. Recommendations are available for fertility preservation of patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to epirubicin may cause fetal harm. Adverse fetal/neonatal effects following in utero exposure to epirubicin during the second and third trimesters include transient ventricular hyperkinesia, transient cardiac enzyme elevation, and a case report of fetal demise due to cardiotoxicity.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of epirubicin may be altered (Janssen 2021; van Hasselt 2014).
The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it is contraindicated in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery (for adequate maternal and fetal bone marrow recovery); epirubicin should not be administered beyond week 35 of gestation. When indicated, chemotherapy may be administered during the second or third trimester at the same dose and schedule as recommended for nonpregnant patients (ESMO [Loibl 2023]; ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
It is not known if epirubicin is present in human breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for ≥7 days after the last epirubicin dose.
Monitor cumulative (lifetime) anthracycline/epirubicin dose. Baseline and repeated measurements of CBC with differential, LFTs (total bilirubin, ALT, AST), serum creatinine. If at risk for tumor lysis syndrome, monitor serum uric acid, potassium, calcium, phosphate, and serum creatinine after initial dose. Assess left ventricular ejection fraction (LVEF) before and regularly during and after epirubicin treatment. The method used for assessment of LVEF (ECG or MUGA) should be consistent during routine monitoring. Obtain ECG. Verify pregnancy status prior to treatment initiation (in patients who could become pregnant). Monitor injection site during infusion for possible extravasation or local reactions. Monitor for signs/symptoms of tumor lysis syndrome. Monitor for secondary malignancy.
Additional cardiovascular monitoring (ASCO [Armenian 2017], ESC [Lyon 2022]): Comprehensive assessment prior to treatment, including a history and physical examination and screening for cardiovascular disease risk factors, such as hypertension, diabetes, dyslipidemia, obesity, and smoking; echocardiogram (transthoracic preferred, perform at baseline and 12 months after therapy completion for all patients; in addition, perform every 2 cycles and within 3 months after therapy completion for high- or very high-risk patients). Cardiac biomarkers (troponin and natriuretic peptide at baseline for high and very high-risk patients [may consider for low- and moderate-risk]; also prior to each cycle during anthracycline treatment and at 3 and 12 months after therapy completion for high- and very high-risk patients). In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or multigated acquisition (MUGA) scan may be utilized; obtain serum cardiac biomarkers. Refer to a cardiologist when clinically indicated.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Epirubicin is an anthracycline antineoplastic agent; known to inhibit DNA and RNA synthesis by steric obstruction after intercalating between DNA base pairs; active throughout entire cell cycle. Intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Also inhibits DNA helicase, and generates cytotoxic free radicals.
Distribution: Vdss: 21 to 27 L/kg
Protein binding: ~77% to albumin
Metabolism: Extensively via hepatic and extrahepatic (including RBCs) routes
Half-life elimination: Triphasic; Mean terminal: 33 hours
Excretion: Feces (34% to 35%); urine (20% to 27%)
Altered kidney function: Clearance was reduced by 50% in patients with serum creatinine ≥5 mg/dL.
Hepatic function impairment: Clearance was reduced by ~30% in patients with elevated AST levels and normal bilirubin, and by ~50% in patients with elevated AST and bilirubin levels, as compared to patients with normal hepatic function.
Older adult: Plasma clearance of epirubicin in elderly female patients was reduced by 35% as compared to younger female patients.
